DT-Web

DB01155 - Gemifloxacin


Identification
Name Gemifloxacin
Accession Number DB01155 (APRD00053)
Type small molecule
Description Gemifloxacin is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. Gemifloxacin acts by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV, which are essential for bacterial growth.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 389.3809
Groups approved
Monoisotopic Weight 389.149932358
Pharmacology
Indication For the treatment of bacterial infection caused by susceptible strains such as S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis, S. pneumoniae (including multi-drug resistant strains [MDRSP]), M. pneumoniae, C. pneumoniae, or K. pneumoniae.
Mechanism of action The bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Absorption Rapidly absorbed from the gastrointestinal tract. The absolute bioavailability averages approximately 71%.
Protein binding 60-70%
Biotransformation Gemifloxacin is metabolized to a limited extent by the liver. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin.
Route of elimination Gemifloxacin and its metabolites are excreted via dual routes of excretion.Following oral administration of gemifloxacin to healthy subjects, a mean (? SD) of 61 ? 9.5% of the dose was excreted in the feces and 36 ? 9.3% in the urine as unchanged drug and metabolites. The mean (? SD) renal clearance following repeat doses of 320 mg was approximately 11.6 ? 3.9 L/hr (range 4.6-6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin.
Toxicity Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Aluminium Formation of non-absorbable complexes
Calcium Acetate Calcium salts such as calcium acetate may decrease the absorption of quinolone antibiotics such as gemifloxacin. Of concern only with oral administration of both agents. Interactions can be minimized by administering oral quinolone at least 2 hours before, or 6 hours after, the dose of an oral calcium supplement. Monitor for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements.
Iron Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Magnesium salicylate Formation of non-absorbable complexes
Sucralfate Formation of non-absorbable complexes
Zinc Formation of non-absorbable complexes
Food Interactions
  • Take without regard to meals.

Targets


DNA topoisomerase 4 subunit A
Name DNA topoisomerase 4 subunit A
Gene Name parC
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Alkorta M, Gimenez MJ, Vicente D, Aguilar L, Perez-Trallero E: In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. Int J Antimicrob Agents. 2005 Feb;25(2):163-7. - Pubmed
  • Yague G, Morris JE, Pan XS, Gould KA, Fisher LM: Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob Agents Chemother. 2002 Feb;46(2):413-9. - Pubmed
  • LaPlante KL, Rybak MJ, Tsuji B, Lodise TP, Kaatz GW: Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. Antimicrob Agents Chemother. 2007 Apr;51(4):1315-20. Epub 2007 Feb 12. - Pubmed
DTHybrid score 0.7501
DNA gyrase subunit A
Name DNA gyrase subunit A
Gene Name gyrA
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Ruiz J, Marco F, Sierra JM, Aguilar L, Garcia-Mendez E, Mensa J, Jimenez De Anta MT, Vila J: In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene. Int J Antimicrob Agents. 2003 Jul;22(1):73-6. - Pubmed
  • Alkorta M, Gimenez MJ, Vicente D, Aguilar L, Perez-Trallero E: In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. Int J Antimicrob Agents. 2005 Feb;25(2):163-7. - Pubmed
  • Yague G, Morris JE, Pan XS, Gould KA, Fisher LM: Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob Agents Chemother. 2002 Feb;46(2):413-9. - Pubmed
DTHybrid score 0.7878

Predictions


Id Partner name Gene Name Score
6224 DNA gyrase subunit A gyrA 0.7878
886 DNA topoisomerase 4 subunit A parC 0.7501
6226 DNA topoisomerase 4 subunit A parC 0.7501
817 DNA topoisomerase 2-alpha TOP2A 0.3509
4200 Cytochrome P450 1A2 CYP1A2 0.1333
118 Organic cation/carnitine transporter 2 SLC22A5 0.0738
1729 Solute carrier family 22 member 6 SLC22A6 0.0655
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0584
1588 Multidrug resistance protein 1 ABCB1 0.0411
4512 Cytochrome P450 3A4 CYP3A4 0.0309
833 Organic cation/carnitine transporter 1 SLC22A4 0.0292
862 Multidrug resistance-associated protein 1 ABCC1 0.024
6144 Solute carrier family 22 member 2 SLC22A2 0.0239
6107 Cytochrome P450 3A7 CYP3A7 0.021
4118 Cytochrome P450 3A5 CYP3A5 0.0197
5718 Cytochrome P450 2A6 CYP2A6 0.0098
6024 Cytochrome P450 1A1 CYP1A1 0.0094
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